Silibinin-induced endoplasmic reticulum stress and mitochondrial dysfunction suppress growth of endometriotic lesions

Jiyeon Ham, Jonggun Kim, Fuller W. Bazer, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticle

Abstract

Silibinin is a flavonolignan extracted from milk thistle, which has been used for treating liver disorders, various cancers, and gynecological diseases. However, attempts for treating endometriosis with silibinin are lacking. In this study, we observed that silibinin exerts antiproliferative and apoptotic effects on human endometriotic cell lines VK2/E6E7 and End1/E6E7. We also identified that silibinin-induced oxidative stress and lipid peroxidation in human endometriotic cells. Moreover, we observed upregulation of calcium concentration in the cytosol and mitochondrial matrix, which resulted in mitochondrial dysfunction. Furthermore, induction of endoplasmic reticulum stress signals with rapid mitogen-activated protein kinase (MAPK) pathway signaling resulted in apoptosis of both cells. Using an animal model mimicking the retrograde menstruation hypothesis, we verified the effects of silibinin on reducing endometriotic lesions by inhibiting the expression of inflammatory cytokines in mice. Silibinin might be used as a novel therapeutic agent or supplement for inhibiting progression of endometriosis in vitro and in vivo.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - 2018 Jan 1

Fingerprint

Endoplasmic Reticulum Stress
Growth
Endometriosis
Flavonolignans
Menstruation Disturbances
Milk Thistle
Oxidative stress
Mitogen-Activated Protein Kinases
Liver
Cytosol
Lipid Peroxidation
silybin
Animals
Oxidative Stress
Up-Regulation
Animal Models
Cells
Apoptosis
Cytokines
Calcium

Keywords

  • apoptosis
  • endometriosis
  • endoplasmic reticulum (ER) stress
  • ROS
  • silibinin

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Silibinin-induced endoplasmic reticulum stress and mitochondrial dysfunction suppress growth of endometriotic lesions. / Ham, Jiyeon; Kim, Jonggun; Bazer, Fuller W.; Lim, Whasun; Song, Gwonhwa.

In: Journal of Cellular Physiology, 01.01.2018.

Research output: Contribution to journalArticle

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